Principles of General Physiology

Note that although the electrical changes were opposite in sign in a and 6, no difference was to he noticed in the nature of the beat, so far as could be judged by the eye. wave, which seems improbable. On the other hand, the fact that, as shown in curve C, this fourth phase, as well as the third, is absent when the wave disappears before it reaches the second electrode, indicates that it is due to a disturbance, excitatory or inhibitory, which travels along the ureter. If it were an inhibition controlled by nerve centres, as in the intestine, it might perhaps have a different time course from the wave of contraction, but it would seem useless for it to follow the contraction wave at the further electrode. The inhibition wave sometimes occurs independently of the excitation, so that a series of monophasic responses in the positive direction may be seen, only occasionally followed by a negative one. The monophasic nature is due to the disappearance of the wave in a region of decrement before it reaches the second electrode.

In the spontaneous peristaltic waves in the crop of Aplysia, it was shown by Dittler (1911) that each wave consists of a simple negative change, without the electropositive accompaniment of that of the ureter. This wave is very FIG. 210. TYPICAL FORM OF THK HUMAN ELECTRO-CARDIOGRAM, AS OBTAINED BY LEADING OFF FROM RIGHT ARM AND LEFT ARM (LEAD 2). E, Electro-cardiogram, with the designation of the component parts or waves as given by Einthoven. Einthoven regards P as the only component belonging to the auricle, Q, Ji, S, T all being parts of the ventricular complex (see text, page 655).

slow, the total duration being about fourteen seconds, but it gives no indication of being anything but a single contraction, not a short tetanus. So far as could be made out, the duration of the mechanical response appeared to coincide with that of the electrical one ; so that, if the latter is an expression of the excitatory state, and not of the state of contraction, the excitatory state in this case, at all events, must not merely precede that of contraction but last as long as the latter does.

The Heart. — Apart from the interest of the phenomenon itself, the electrical change in the heart has become of great importance, not only as a means of following the course of the contraction, but as a clinical method of investigating irregularities in the heart beat (see the book by Lewis, 1913). v An exact analysis of the electrical change was first made by Burdon-Sanderson and Page (1880), who showed that, in the frog's ventricle, a diphasic deflection occurred, similar to that which we have described in nerve and muscle. This was of such a direction as to show that the excitation process started at the base, and progressed as a wave to the apex. Fig. 208 is a photograph by Gotch (1910) of the phenomenon in the tortoise. In this case one electrode was on the auricle, the other on the apex of the ventricle, so that the auricular change is also shown, and is seen to be similar to that of the ventricle, but smaller. I made, in conjunction with Starling (1892, 1), Observations on the corresponding change in the

mammalian heart. When electrodes were placed on the base and apex of the ventricle, in as normal a condition as we could maintain it, we found that the electrical change was of a simple diphasic character, indicating that the wave started at the base and was propagated to the apex, as shown in Fig. 209 (curve a). When, however, the phenomenon was investigated without opening the chest, as can be done by leading off from the right arm and left leg, there was found to be a third phase present, in the same direction as the first. The explanation which we gave was that the excitation process lasts longer at the base than at the apex, so that the electrical negativity at the apex has disappeared before that at the base has completed its time course. The subject was taken up by Einthoven, who invented the string galvanometer (1901, 1903, and 1904) for the purpose of the work. Fig. 210 shows the human "electro-cardiogram," with the designations of the components used by Einthoven (1913). It has been clearly shown that the first wave, P, is due to the auricular contraction, the second phase of the auricular contraction is usually concealed by the commencement of the first ventricular phase, R. The meaning of the small change, Q, is rather doubtful; it is not always present, and appears to belong to the ventricular "complex," as it is called. If so, it may mean that the ventricular excitation wave starts from a point a little distant from the base, or it may be merely a branch current, as it is so minute. The ventricular complex consists of the three deflections, R, s, and T. The first

FIG. 211. EFFECT OF LOCAL WARMING ON THE ELECTRICAL CHANGE IN THE The first and last parts of the tracing show the normal diphasic effect before and after warming the apex. The second and third parts show the effect of shortening the duration of the excitatory process at the apex by raising the temperature. The relatively greater duration of the process at the base causes the appearance of the third phase, corresponding to Einthoven's T wave. The way in which this happens is shown in Fig. 212.

two obviously represent the commencement of the wave at, or near, the base and its progress to, and arrival at, the apex. But why is it cut short so quickly and followed by the third phase, which indicates excitation at the base 1 It is clear that the equipotential interval between s and T must mean that the whole ventricle is in a state of excitation ; in fact, it corresponds to that part of the mechanical curve of the heart beat in which the entire ventricle is in a state of contraction. In further analysis, there are some facts to which Mines (1913, 3) calls attention, in a paper which contains an admirable account of the electrocardiogram. There is no reason to suppose that the t wave . is of any different nature from that of the other parts of the complex. It is the end of the total change, as shown by comparison with the monophasic change obtained when the one electrode is on an injured spot. As mentioned above, Bayliss and Starling (1892, 1) pointed out that it must be due to the electrical change at the base lasting longer than at the apex. It is in the same direction as the initial effect, R. This conclusion is confirmed by Mines (1913, 3, p. 201) in experiments in which, by warming the apex of the frog's ventricle, when it was giving a diphasic change, he caused the effect at the latter to take on a more rapid time course, and thus made the base negativity to last relatively longer. Fig. 211 shows that a curve similar to that of the human electro-cardiogram is obtained. But why, in the normal heart, should the base, which is excited first, apparently remain excited last1? Gotch (1910) thought that it was due to the wave leaving the base, passing to the apex, and then back again to the base at the origin of the aorta. He brought it into relation with the development of the heart from a folded tube in the embryo.

Meek and Eyster (1912) and Mines (1913, 3) have shown, however, that such an explanation does not hold. Details may be found in the work of Mines, who followed the course of the excitation wave by leading off from various points on the surface of the ventricle in the frog. No evidence was obtained of such a course of the wave as that supposed by Gotch. The only satisfactory explanation was found to be that the negativity at the base does actually last longer than that at the apex, when the heart is in position in the intact animal. The way in which this fact accounts for the form of the electro-cardiogram will be clear from Fig. 212.

Now we must remember that, in the mammalian heart, the auricular excitation is transmitted to the ventricle through a system of special muscular fibres, Purkinje's cells, which branch to all parts of the ventricle, and that the muscular structure of the contractile wall consists of strands passing in various directions. It seems that Einthoven is inclined to attribute the form of the electrocardiogram to excitation starting from a place not exactly at the base, but reaching the base before the apex, although various other parts, not necessarily the apex, might be excited immediately after the base. However the excitation wave is conveyed, it seems that at any given spot all the muscular layers must be in contraction s'multaneously, otherwise there would be danger of their tearing apart. Moreover, the fact that simple hearts, such as those of the frog and tortoise, show, in the intact animal, similar forms of electro-cardiogram to that of the mammal, indicates that the development of the Purkinje system does not alter the general course of the wave. Electro-cardiograms of some of the lower vertebrates are given in Fig. 213 (from Lewis's book). It is probable, as Mines points out (1913, 3, p. 208), that the state of excitation lasts so much longer than the time taken for its transmission from one part to another, that a very small difference in the duration at one point or another

is sufficient to determine the sign of the final phase. In fact, he noticed an alteration of sign in the final phase in a tortoise heart without any obvious difference in the beat. A detailed analysis of the course of the excitation wave in the dog and in the toad is given in the papers by Thos. Lewis (1915, 1 and 2). From what has been stated, it will be clear that the chief practical value of the electro-cardiogram is in the detection of abnormalities in transmission from auricle to ventricle. Especially is it to be noted that conclusions based on changes in form of the ventricular complex rest on an uncertain basis until we know more about the precise meaning of its components. The very smallest difference between the time at which the excitation wave reaches two points decides which of these becomes negative first, although, as regards the mechanism of the contraction, the fact may be of no significance (see especially Figs. 209 and 211). There is, it may be repeated, no evidence that any component of the electro-cardiogram is due to. a process different from any other component.

Such a condition is brought about by wanning the apex, for example. The uppermost curve represents the excitatory state (negativity) at the base. The middle one, that at the apex ; represented in the opposite direction, since the ventricle is supposed to be led off by electrodes at base and apex. The lowest curve represents the electrical change which would be seen with the capillary electrometer. The whole is to be explained by difference in time relations of the ordinary wave of excitation in different directions. Caution must be exercised in drawing conclusions from the signs of the components. The electrical change, as recorded, does not merely indicate the magnitude of the process under one electrode only, since electrical expression of it is cut short according to the time at which the wave arrives at the other electrode.

The relations in time of the mechanical and electrical effects are of some Frog, goldfish, pigeon, and tortoise in order from above downwards. The essential similarity to the human electro-cardiogram will be noticed in the cases of the frog and the tortoise. The goldfish shows a diphasic ventricular change, like the exposed heart of the frog and tortoise. That of the pigeon is peculiar. interest. Figs. 172, 173, and 214 show that the duration is practically identical. In Fig. 214, from a short article by Piper (1913, 1), we see that the latter begins a little before the pressure change, and ends a little earlier. An interesting point is that the greater part of the final electrical phase appears to take place after the pressure curve has begun to fall, a fact which tends to confirm the view taken above that it represents the last part of the wave of excitation, namely, that part in the fibres which are the latest to relax.

It has been remarked above (page 215) that Lovatt Evans (1912, 2) found that the heart of the snail, although requiring calcium for its normal activity, is unusually insensitive to these ions. Thus, with 1 per cent, calcium chloride the beat is normal, while the frog's heart is sent into systolic contraction by this concentration. A peculiar effect on the electro-cardiogram is also to be seen. In Fig. 215 we see the effect referred to. The heart is first in tonus ; calcium

chloride, 0'6 per cent., is then applied, and subsequently a regular series of beats with a large initial deflection made its appearance. This disappeared again when the calcium salt was washed away with sodium chloride. The electro-positive change occurring in inhibition, observed by Gaskell and others (p. 407), has been already discussed. Secreting Glands. — The electrical changes in the salivary glands have been described above (pages 350-352). Fig. 93 (page 351) represents them. Certain conclusions as to the secretory process were drawn from them. Electrical effects in other glands were also mentioned, especially those of Hermann and Luchsingef on the frog's tongue and on the sweat glands of the cat (1878, 1 and 2).

The skin of the frog is also a structure containing simple glands, on which considerable work has been done. That of L. and E. Orbeli (1910), which contains full references to the earlier work, may be especially referred to here. These observers show that the direction of the response to nerve stimulation varies with the solution used on the leading off electrodes. With water alone the current is an inflowing one, that is, the outer surface becomes negative ; with sodium chloride, 0-055 to 0'7 per cent., it becomes positive. With potassium chloride the effect is the same as with water, but preceded by a small deflection in the opposite direction. The interpretation of the facts is not easy, but the occurrence of an electrical change in the presence of water electrodes shows that it is not merely due to the ions of the electrodes. Also, the occurrence of two changes in two different directions indicates the existence of two processes in the gland cells, as discussed above (page 352).

If we suppose that we lead off from opposite ends of a gland cell and that one end becomes permeable when secretion occurs, it is clear that we obtain then the potential of the Helmholtz double layer, since we obtain access, as it were, to the interior of the cell. Thus, if the cell membrane is, at rest, permeable to certain anions only, we obtain an effect of the sign of that associated with stimulation of the chorda tympani nerve in the dog. This view is in agreement with the theory of secretion given above (page .'5."> I ).

Electrical Fish. — The capability of certain fishes to give powerful electric shocks, amounting to a potential difference of two or three hundred volts, might appear puzzling until we remember that the electric organs are composed of a large number of plates, arranged in series, and that these plates are excited simultaneously by nerve fibres, so that a certain small potential difference is established between the opposite sides of each plate. We see that there is no wave of excitation and, experimentally, the electrical change is found to be a discharge, or series of rhythmic discharges, in one direction only.

With the exception of that of Malapterurus, the electrical organs appear to be formed of modified skeletal muscle. It has been suggested by Gotch that the electrical change is that of the nerve end-plate. The muscular structure itself has almost disappeared, but Fig. 216 shows that an apparently complex arrangement of papillae has taken its place. It is interesting to note that, although the organ of Malapterurus is developed from skin glands, its structure is very similar to that of other fish, so that there must be some significance in those parts present in addition to the nerve end-plaAes of the original muscle fibres.

truths of a second. Note that the electrical change continues during The electromotive force of the shock, owing to the manner of connection of the plates in series, is naturally greater when these plates are arranged along the length of the fish than when across it. That of Malapterurus, according to the most recent determinations of Cremer, with the string galvanometer (see Garten's article, 1910, p. 200), amounts to 450 volts. It is obvious that, in order to obtain an effective potential difference, the whole of the electrical plates must be excited simultaneously. When they are all innervated from a single neurone on each side, as in Malapterurus (see page 471 above), this is easily explained. But in other fish the centres consist of a large number of cells, 106,000 in T<*rpedo, according to Fritsch. Since each single discharge of the organ only lasts about 0'005 sec., the adjustment of the reflex activity of the neurones must be very accurate in order that each plate shall be in phase with the others, so as to sum up with them.

The latent period appears to be no less when the organ is stimulated directly than when through the nerve. This fact may mean that the only active part is the nerve end-plate, or that any other part, such as might be developed out of the muscle fibre, is not directly excitable. After section of the nerves, the direct and indirect excitability of the organ vanish together, contrary to the case of muscle. That there is something more than nerve fibre responsible for the

electrical change is shown by the fact that the organ is much more quickly fatigued than nerve fibre itself, although not so quickly as muscle (Garten, 1910, p. 184). The fatigue is simultaneous for direct and indirect stimulation, and is thus situated in the active cells themselves, not in an intermediate substance. Experiments on heat production have shown that it is very minute ; but the results are somewhat contradictory, and it has been suggested that two processes may be going on, an endothermic and an exothermic one. Correspondingly, only

The conclusion seems to be indicated that the process is one involving very slight expenditure of energy, apart from that necessary for the current itself. Probably the chief process is one of change of permeability, involving redistribution of ions. The electric fish are relatively insensitive to electrical shocks, although not entirely so, as was thought at one time. This state may, perhaps, depend on some peculiarity of the permeability of their cell membranes to ions ; that is, it may be a bad electrolytic conductor, as suggested by Garten (1910, p. 212).

The, Retina. — The significance of the electrical change in this organ has been discussed above (pages 523-524). Plant Tissues. — In accordance with the general theory of the mode of production of differences of electrical* potential, it would be expected that all phenomena associated with changes in the permeability of the cell membrane would give rise to electrical effects. Owing to the short circuits present in all tissues, it is only when the processes take place with some rapidity that it is possible to detect them.

Some cases have already been given. Dionsva and the sensitive plant (page 430), the effect of light on the green leaf (page 567), and the moving protoplasm of Nitella may be mentioned. Loeb and Beutner (1912) and Beutner (1912) made some interesting experiments on the apple. Tf both electrodes are on uninjured surfaces, change of the electrolyte concentration in one of the electrodes causes the appearance of a potential difference, owing to change of concentration of the ions forming the double layer, and the magnitude of the effect follows the Nernst The addition of non - electrolytes, urea

SKATK. — Microscopic structure of part of one of the discs. Somewhat diagrammatic. A, Transverse septum at its junction with the longitudinal septum ; a nerve is seen in section. or sugar, does not affect the potential difference. All cations act in the same way, as was explained above (page 161), owing to the possibility of free interchange between ions of the same sign. It may be remarked that interchangeability as regards all cations distinguishes the kind of concentration battery in question from that where metallic electrodes are concerned. In the latter case, of course, it applies only to salts of the particular metallic ion itself. In the former case, the electrode, by interchange, becomes one composed of all the cations present outside it, in corresponding concentrations.

The reader will probably have noticed how much of the fundamental work in the region of the phenomena of electrical responses is due to Burdon- Sanderson and his co-workers. Skeletal muscle, heart, plant tissue, and the electric fish received the greater part of their clear and definite presentation from the researches mentioned. This is, therefore, the most appropriate place to call attention to his portrait, which will be found in Fig. 217. In the use of instruments for recording the changes in the electrical state of tissues, the important point to be kept in mind is that the moving parts shall be able to follow rapid alterations in current or potential, and this without overshooting the correct position. They must either be aperiodic, but without more damping than just necessary, or their own vibration period must be shorter than that of any change to be measured.

The interest of electrical changes is not only as giving insight into the processes going on in the cells, but also as a means of investigation of the time relations and other properties of these processes. In the case of nerves, there is frequently no other method available for detecting the existence of the passage of impulses. Although the ultimate source of differences of potential in cells must be due to the separation of electrically charged ions, it is found that the different rates of movement of ions free to diffuse is inadequate, while the presence of metallic electrodes similar to those of the usual form of concentration battery is out of the question.

On the other hand, the existence of a cell membrane permeable to one only of the oppositely charged ions of a binary electrolyte is capable of accounting satisfactorily for all the phenomena met with. It is shown that the electromotive force of a concentration battery of this particular kind follows the same formula as that with metallic electrodes. It may, indeed, be regarded as a model of the process in, the case of metallic electrodes. The difference is that the membrane cell, or electrode, is indifferent to the chemical nature of the ions, being concerned only with the sign of the charge, while the metallic electrode only takes account of ions of the same chemical nature as itself. The reason for this difference in behaviour is that the membrane allows free interchange between diffusible ions of the same sign between the interior and exterior, so long as the potential difference is unchanged thereby.

The contact surface between phases is, similarly, the site of a potential difference, if one of the ions is soluble in both phases, the other in one only. There is reason to believe that the electrical change in nerve and muscle is inseparable from the state of excitation, but that the state of contraction of muscle may be absent, although the electrical phenomena remain. Description is given in the text of the way in which the " demarcation current " and the " negative variation " in nerve and muscle are explained on the basis of membrane potential.

In the ventricle of the heart, when led off directly, there is a simple diphasic change, indicating the progression of a wave of negativity from base to apex. When the electro-cardiogram is obtained from the unexposed heart it has hree phases, the third one indicating negativity of the base. This may be due either to the excitatory state lasting longer at the base than at the apex, or be due to the course of the wave not being so simple as a progression from base to apex merely. The former hypothesis is more in accordance with facts. But it must be remembered that transmission is by means of Purkinje tissue, which conducts faster than ordinary heart muscle, so that contraction may be practically simultaneous in all parts of the ventricle. By shortening, artificially, the duration of the excitatory state at the apex, or lengthening that at the base, the triphasic curve can be obtained from a diphasic one.